Although hypothalamic neurons can be driven powerfully by nociceptive and other forms of somatosensory stimulation, the spinal input to this region has been generally believed to be multisynaptic. However, we have recently found that a large number of spinal cord neurons project directly to the hypothalamus and telencephalon in rats. Injections of any of three different retrograade tracers that were restricted to the hpothalamus labeled many neurons in the spinal cord. Labeled neurons were found primarily within the marginal zone, the lateral reticulated area (lamina V), the gray matter surrounding the central canal and the lateral spinal nucleus. Based on the results of such injections we have determined that there are more than 5000 neurons throughout the length of the spinal cord that project to the hypothalamus. Injections of the anterograde tracer PHAL into the spinal cord labeled fibers and varicosities in a number of hypothalamic nuclei and also within several telencephalic areas including the basal forebrain, septal nuclei and nucleus accumbens. Injections of retrograde tracers that were restricted to each of these telencephalic areas also labeled spinal cord neurons. We have physiologically examined 10 neurons thatat were antidromically activated wih low intesity current from the hypothalamus. All 10 responded to innocuous mechanical stimuli but responded more vigorously to noxious mechanical and thermal stimulation. In the proposed studies we will 1) continue our physiological studies of spinal cord nuerons that are antidromically activated from the hypothalamus, 2) physiologically examine spinal cord neurons that project to telencephalic nuclei, 3) determine the course of the axons within the spinal cord as they ascend to the hypothalamus and telencephalon, 4) use retrograde labeling techniques to determine if similar projections exist in cats and 5) determine if similar projections exist in monkeys using retrograde tracers. If such projections are found in monkeys, we will determine the distribution of their terminations within the hypothalamus and telencephalon and their course within the spinal cord. In addition, the response properties of their cells or orgin will be determined to a variety of innocuous and noxious cutaneous stimuli. These studies will provide important data on the spinal cord neurons that project directly to areas that are involved in autonomic, neuroendocrine and affective responses to nociceptive and other forms of somatosensory stimulation.